Denervation of a skeletal muscles results in a selective accumulation of interstitial cells in the junctional region of the muscle. The interstitial cells, which are antigenically and morphologically similar to fibroblasts, may well play a role in the regeneration of the neuromuscular junction. The aims are to identify the source of the interstitial cells, to determine the influence of nerve activity on the generation of the cell accumulation, and to determine the contribution of the interstitial cells to the regeneration process. The interstitial cells may participate in the redistribution of extracellular matrix and cell adhesion molecules in denervated muscle, the growth of regenerating axons or the stability of regenerated nerve terminals. The methods used in this study include immunohistochemistry, light and electron microscopy, tissue culture techniques and production of monoclonal antibodies. When nerves innervating muscles are damaged, all movement is lost. Although with time axons regrow to reestablish connections with muscle, movement is seldom completely restored. The studies described here will provide new and important information about the degeneration process in skeletal muscle and contribution of the interstitial cell accumulation. Such information is essential for the development and study of methods to enhance axonal regeneration.